Diethyl Ether → 4-{3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-heptan-4-ol

HRID 1432682Notes

Reaction equation

HRID 1432682 reaction equation
[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([C:22](=[O:26])[CH2:23][CH2:24][CH3:25])[C:16]2=[N:15][C:14]=1[CH3:28].[CH2:29]1[CH2:33]OC[CH2:30]1.C([Mg]Br)CC.C(OCC)C>C(OCC)(=O)C>[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([C:22]([OH:26])([CH2:30][CH2:29][CH3:33])[CH2:23][CH2:24][CH3:25])[C:16]2=[N:15][C:14]=1[CH3:28]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 579330721-{3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-butan-1-oneHCID 178455851HCID 178455851, compound

Product 1

HCID 579329174-{3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-heptan-4-olYield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-{3-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-butan-1-one (0.15 g, 0.36 mmol) and THF (5 mL) is cooled to 0° C., and a 2.0 M propyl magnesium bromide solution in diethylether (0.22 mL, 0.43 mmol) is added. The reaction is warmed to ambient temperature, diluted with ethyl acetate (30 mL), and washed with a sat. NH4Cl solution (30 mL). The organic layer is dried over MgSO4, filtered, and concentrated. The residue is purified by ISCO flash chromatography (20%-40% EtOAc gradient) to furnish the title compound (0.016 g, 0.017 mmol, 47%). 1H-NMR (CDCl3), δ 0.90 (t, J=7.4 Hz, 6H), 1.12-1.29 (m, 2H), 1.37-1.54 (m, 2H), 1.86-2.04 (m, 4H), 2.50 (s, 3H), 2.54 (s, 3H), 4.15 (s, 3H), 6.11 (bs, 1H), 6.73 (s, 1H), 7.48 (s, 1H), 7.90 (s, 1H) ppm. LC/MS (m/z): calcd. for C22H27ClN6OS (M+H)+: 459.2; found: 459.3.

Workup

  1. washwashed with a sat. NH4Cl solution (30 mL)
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO flash chromatography (20%-40% EtOAc gradient)

Sources & evidence

ORD record
ord-511f200c3337409492f1104eedb40029
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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